2021
Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms
Song E, Bartley CM, Chow RD, Ngo TT, Jiang R, Zamecnik CR, Dandekar R, Loudermilk RP, Dai Y, Liu F, Sunshine S, Liu J, Wu W, Hawes IA, Alvarenga BD, Huynh T, McAlpine L, Rahman NT, Geng B, Chiarella J, Goldman-Israelow B, Vogels CBF, Grubaugh ND, Casanovas-Massana A, Phinney BS, Salemi M, Alexander JR, Gallego JA, Lencz T, Walsh H, Wapniarski AE, Mohanty S, Lucas C, Klein J, Mao T, Oh J, Ring A, Spudich S, Ko AI, Kleinstein SH, Pak J, DeRisi JL, Iwasaki A, Pleasure SJ, Wilson MR, Farhadian SF. Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms. Cell Reports Medicine 2021, 2: 100288. PMID: 33969321, PMCID: PMC8091032, DOI: 10.1016/j.xcrm.2021.100288.Peer-Reviewed Original ResearchNeurological symptomsImmune responseCerebrospinal fluidAnti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodiesCOVID-19Self-reactive immune responsesSARS-CoV-2 antibodiesCompartmentalized immune responseCSF immunoglobulin GRole of autoimmunityCOVID-19 patientsB cell responsesCoronavirus disease 2019Immune surveyNeurologic sequelaePulmonary infectionBrain infectionSerum antibodiesDisease 2019Monoclonal antibody targetsAnimal modelsTarget epitopesCell activationCell responsesSingle-cell RNA sequencingDiverse functional autoantibodies in patients with COVID-19
Wang EY, Mao T, Klein J, Dai Y, Huck JD, Jaycox JR, Liu F, Zhou T, Israelow B, Wong P, Coppi A, Lucas C, Silva J, Oh JE, Song E, Perotti ES, Zheng NS, Fischer S, Campbell M, Fournier JB, Wyllie AL, Vogels CBF, Ott IM, Kalinich CC, Petrone ME, Watkins AE, Dela Cruz C, Farhadian S, Schulz W, Ma S, Grubaugh N, Ko A, Iwasaki A, Ring A. Diverse functional autoantibodies in patients with COVID-19. Nature 2021, 595: 283-288. PMID: 34010947, DOI: 10.1038/s41586-021-03631-y.Peer-Reviewed Original ResearchConceptsPeripheral immune cell compositionSARS-CoV-2 infectionCOVID-19Effects of autoantibodiesTissue-associated antigensSpecific clinical characteristicsInnate immune activationImmune cell compositionCOVID-19 exhibitCOVID-19 manifestsAnalysis of autoantibodiesSARS-CoV-2Functional autoantibodiesMouse surrogateClinical characteristicsVirological controlClinical outcomesImmune activationMild diseaseAsymptomatic infectionAutoantibody reactivityDisease progressionHealthcare workersHigh prevalenceAutoantibodiesDelayed production of neutralizing antibodies correlates with fatal COVID-19
Lucas C, Klein J, Sundaram ME, Liu F, Wong P, Silva J, Mao T, Oh JE, Mohanty S, Huang J, Tokuyama M, Lu P, Venkataraman A, Park A, Israelow B, Vogels CBF, Muenker MC, Chang CH, Casanovas-Massana A, Moore AJ, Zell J, Fournier JB, Wyllie A, Campbell M, Lee A, Chun H, Grubaugh N, Schulz W, Farhadian S, Dela Cruz C, Ring A, Shaw A, Wisnewski A, Yildirim I, Ko A, Omer S, Iwasaki A. Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nature Medicine 2021, 27: 1178-1186. PMID: 33953384, PMCID: PMC8785364, DOI: 10.1038/s41591-021-01355-0.Peer-Reviewed Original ResearchConceptsDeceased patientsAntibody levelsAntibody responseDisease severityAnti-S IgG levelsCOVID-19 disease outcomesFatal COVID-19Impaired viral controlWorse clinical progressionWorse disease severitySevere COVID-19Length of hospitalizationImmunoglobulin G levelsHumoral immune responseCoronavirus disease 2019COVID-19 mortalityCOVID-19Domain (RBD) IgGSeroconversion kineticsDisease courseIgG levelsClinical parametersClinical progressionHumoral responseDisease onset
2020
SalivaDirect: A simplified and flexible platform to enhance SARS-CoV-2 testing capacity
Vogels CBF, Watkins AE, Harden CA, Brackney DE, Shafer J, Wang J, Caraballo C, Kalinich CC, Ott IM, Fauver JR, Kudo E, Lu P, Venkataraman A, Tokuyama M, Moore AJ, Muenker MC, Casanovas-Massana A, Fournier J, Bermejo S, Campbell M, Datta R, Nelson A, Team Y, Anastasio K, Askenase M, Batsu M, Bickerton S, Brower K, Bucklin M, Cahill S, Cao Y, Courchaine E, DeIuliis G, Earnest R, Geng B, Goldman-Israelow B, Handoko R, Khoury-Hanold W, Kim D, Knaggs L, Kuang M, Lapidus S, Lim J, Linehan M, Lu-Culligan A, Martin A, Matos I, McDonald D, Minasyan M, Nakahata M, Naushad N, Nouws J, Obaid A, Odio C, Oh J, Omer S, Park A, Park H, Peng X, Petrone M, Prophet S, Rice T, Rose K, Sewanan L, Sharma L, Shaw A, Shepard D, Smolgovsky M, Sonnert N, Strong Y, Todeasa C, Valdez J, Velazquez S, Vijayakumar P, White E, Yang Y, Dela Cruz C, Ko A, Iwasaki A, Krumholz H, Matheus J, Hui P, Liu C, Farhadian S, Sikka R, Wyllie A, Grubaugh N. SalivaDirect: A simplified and flexible platform to enhance SARS-CoV-2 testing capacity. Med 2020, 2: 263-280.e6. PMID: 33521748, PMCID: PMC7836249, DOI: 10.1016/j.medj.2020.12.010.Peer-Reviewed Original ResearchConceptsEmergency use authorizationSARS-CoV-2 testingSARS-CoV-2 screeningSARS-CoV-2 testing capacitySupply chain shortagesHospital cohortNasopharyngeal swabsHealthy individualsDrug AdministrationHigh positive agreementQRT-PCR assaysDiagnostic testsU.S. FoodSafe reopeningTesting capacityGlobal healthPositive agreementFast GrantLower ratesSalivaNucleic acid extractionSwabsValid alternativeAssay costsCollection tubesSex differences in immune responses that underlie COVID-19 disease outcomes
Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J, Silva J, Mao T, Oh JE, Tokuyama M, Lu P, Venkataraman A, Park A, Liu F, Meir A, Sun J, Wang EY, Casanovas-Massana A, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Shaw A, Fournier J, Odio C, Farhadian S, Dela Cruz C, Grubaugh N, Schulz W, Ring A, Ko A, Omer S, Iwasaki A. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature 2020, 588: 315-320. PMID: 32846427, PMCID: PMC7725931, DOI: 10.1038/s41586-020-2700-3.Peer-Reviewed Original ResearchConceptsInnate immune cytokinesFemale patientsMale patientsImmune cytokinesDisease outcomeImmune responseCOVID-19COVID-19 disease outcomesPoor T cell responsesSARS-CoV-2 infectionSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusSex-based approachModerate COVID-19Sex differencesRobust T cell activationT cell responsesWorse disease progressionWorse disease outcomesHigher plasma levelsNon-classical monocytesCoronavirus disease 2019T cell activationImmunomodulatory medicationsPlasma cytokinesLongitudinal analyses reveal immunological misfiring in severe COVID-19
Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B, Takahashi T, Tokuyama M, Lu P, Venkataraman A, Park A, Mohanty S, Wang H, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Muenker MC, Fournier JB, Campbell M, Odio CD, Casanovas-Massana A, Herbst R, Shaw A, Medzhitov R, Schulz W, Grubaugh N, Dela Cruz C, Farhadian S, Ko A, Omer S, Iwasaki A. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020, 584: 463-469. PMID: 32717743, PMCID: PMC7477538, DOI: 10.1038/s41586-020-2588-y.Peer-Reviewed Original ResearchConceptsSevere COVID-19Moderate COVID-19Immune signaturesDisease outcomeCOVID-19Disease trajectoriesInterleukin-5Early immune signaturesInnate cell lineagesType 2 effectorsT cell numbersPoor clinical outcomeWorse disease outcomesImmune response profileCoronavirus disease 2019Distinct disease trajectoriesCytokine levelsImmunological correlatesImmune profileClinical outcomesEarly elevationImmune profilingIL-13Immunoglobulin EDisease 2019
2022
Multiscale PHATE identifies multimodal signatures of COVID-19
Kuchroo M, Huang J, Wong P, Grenier JC, Shung D, Tong A, Lucas C, Klein J, Burkhardt DB, Gigante S, Godavarthi A, Rieck B, Israelow B, Simonov M, Mao T, Oh JE, Silva J, Takahashi T, Odio CD, Casanovas-Massana A, Fournier J, Farhadian S, Dela Cruz C, Ko A, Hirn M, Wilson F, Hussin J, Wolf G, Iwasaki A, Krishnaswamy S. Multiscale PHATE identifies multimodal signatures of COVID-19. Nature Biotechnology 2022, 40: 681-691. PMID: 35228707, PMCID: PMC10015653, DOI: 10.1038/s41587-021-01186-x.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingTransposase-accessible chromatinSingle-cell sequencingRNA sequencingBiological insightsPopulation groupingsSophisticated computational toolsBiological featuresSequencingFlow cytometryComputational toolsChromatinBiomedical communityDifferent data typesCell responsesCellsPhate